Pathways mediating resolution of inflammation: when enough is too much

Area of Science:

• Immunology
• Critical Care Medicine
• Pathophysiology

Background:

• Critical illness and sepsis are characterized by profound immune dysregulation.
• Therapeutic strategies have historically focused on pro-inflammatory responses, but immunosuppressive pathways are gaining attention.
• A unifying framework for understanding these immune alterations is lacking.

Purpose of the Study:

• To review the role of pro-resolution pathways in critical illness.
• To propose a novel hypothesis of "injurious resolution" in critical illness.
• To discuss the dysregulation of immune cell processes and their contribution to disease.

Main Methods:

• Literature review of immune function in critical illness and sepsis.
• Analysis of pro-resolution pathways and their contribution to immune alterations.
• Discussion of specific immune cell dysregulations, including neutrophil apoptosis, efferocytosis, myeloid-derived suppressor cells, and T-regulatory cells.

Main Results:

• Immune alterations in critical illness can be viewed as either a failure of inflammation resolution or inappropriate "injurious resolution."
• Dysregulation of neutrophil apoptosis and macrophage efferocytosis are key processes.
• Specialized immune cell subtypes, such as myeloid-derived suppressor cells and T-regulatory cells, play emerging roles.

Conclusions:

• The concept of "injurious resolution" offers a novel framework for understanding immune dysfunction in critical illness.
• Targeting pro-resolution pathways and understanding the roles of specific immune cells may lead to new therapeutic strategies.
• Further research is needed to elucidate the precise mechanisms of immune dysregulation and "injurious resolution" in sepsis and critical illness.